Risk of hypertension higher with DTG in PLWH

In the secondary analysis of the NAMSAL and ADVANCE trials, first-line treatment with dolutegravir (DTG) was associated with significantly higher risks of treatment-emergent hypertension in people living with HIV (PLWH), especially in combination with tenofovir alafenamide (TAF).

“In NAMSAL, about 1 percent of patients had hypertension at study entry but very few were treated,” said Dr Francois Venter from the University of the Witwatersrand, Johannesburg, South Africa, at IAS 2023. “In this study, the risk of hypertension remained higher for the DTG-based regimen through week 192.”

“In ADVANCE, most cases of hypertension were successfully treated. There was no significant difference between treatment arms by week 192,” he continued.

NAMSAL

In this study, 613 treatment-naïve PLWH in Cameroon (median age 37 years, 66 percent female) were randomized 1:1 to receive tenofovir disoproxil fumarate (TDF) and lamivudine with either DTG or low-dose efavirenz (EFV; 400 mg). Thirty-seven percent of participants with obesity had grade 1 hypertension, which was defined as systolic blood pressure (SBP) of 140–159 mm Hg and/or diastolic BP (DBP) of 90–99 mm Hg. Less than 1 percent have received antihypertensive treatment. [IAS 2023, abstract 5640]

Participants continued to gain weight over time, more so with the DTG- vs the EFV-based regimen.

“As weight increased, so did the BP, but it was particularly greater in the DTG arm,” noted Venter. By week 192, the difference in mean SBP between arms was 6.5 mm Hg (p<0.01).

A third of participants on the DTG-based regimen had SBP >140 mm Hg or DBP >90 mm Hg at week 192. The corresponding percentage in the comparator arm was only 19 percent. Between-group comparison yielded a p value of 0.002.

The rates of participants with hypertension were consistently higher with the DTG- vs the EFV-based regimen across all DAIDS* grades: 18 percent vs 13 percent; p=0.002 (grade 1), 8 percent vs 6 percent; p=0.016 (grade 2), and 7 percent vs 2 percent; p=0.004 (grade 3).

ADVANCE

In ADVANCE, 1,053 treatment-naïve PLWH in South Africa (median age 32 years, 59 percent female) were randomized 1:1:1 to receive TAF/emtricitabine (FTC)/DTG, TDF/FTC/DTG, or TDF/FTC/EFV 600 mg. About 10 percent of participants had hypertension at baseline.

There was a consistent increase in weight over time across all arms, with the greatest increase observed with the TAF-based regimen.

“Treatment-emergent grade 1 hypertension was significantly higher with TAF/FTC/DTG vs TDF/FTC/EFV (p=0.038),” said Venter. By week 192, more than half of TDF/FTC/DTG recipients had SBP >130 mm Hg or DBP >85 mm Hg, as opposed to 45 percent in the TDF/FTC/EFV arm (p=0.047).

Hypertension in PLWH needs to be addressed

First-line use of TAF and DTG leads to higher risks of clinical obesity compared with TDF or EFV. Clinical obesity increases the risks of hypertension and other noncommunicable diseases (NCDs). “In both studies, the higher risks of hypertension were due partly to the weight gain on treatment and to ageing,” said Venter.

“Hypertension can be diagnosed and treated with low-cost generic drugs,” noted Venter. “Mass HIV treatment programmes need to include support and funding for diagnosis and treatment for hypertension and other NCDs.”